title: Ectopic KIT copy number variation underlies impaired migration of primordial germ cells associated with gonadal hypoplasia in cattle (Bos taurus).
abstract: Impaired migration of primordial germ cells during embryonic development causes hereditary gonadal hypoplasia in both sexes of Northern Finncattle and Swedish Mountain cattle. The affected gonads exhibit a lack of or, in rare cases, a reduced number of germ cells. Most affected animals present left-sided gonadal hypoplasia. However, right-sided and bilateral cases are also found. This type of gonadal hypoplasia prevails in animals with white coat colour. Previous studies indicated that gonadal hypoplasia is inherited in an autosomal recessive fashion with incomplete penetrance. In order to identify genetic regions underlying gonadal hypoplasia, a genome-wide association study (GWAS) and a copy number variation (CNV) analysis were performed with 94 animals, including 21 affected animals, using bovine 777,962 SNP arrays. The GWAS and CNV results revealed two significantly associated regions on bovine chromosomes (BTA) 29 and 6, respectively (P=2.19 x 10(-13) and P=5.65 x 10(-6)). Subsequent cytogenetic and PCR analyses demonstrated that homozygosity of a ~500 kb chromosomal segment translocated from BTA6 to BTA29 (Cs29 allele) is the underlying genetic mechanism responsible for gonadal hypoplasia. The duplicated segment includes the KIT gene that is known to regulate the migration of germ cells and precursors of melanocytes. This duplication is also one of the two translocations associated with colour sidedness in various cattle breeds.
authors.affiliation: Department of Production Animal Medicine, University of Helsinki, Saarentaus, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Venhoranta
authors.forename: Hubert
authors.initials: H
authors.lastname: Pausch
authors.forename: Michal
authors.initials: M
authors.lastname: Wysocki
authors.forename: Izabela
authors.initials: I
authors.lastname: Szczerbal
authors.forename: Reetta
authors.initials: R
authors.lastname: Hänninen
authors.forename: Juhani
authors.initials: J
authors.lastname: Taponen
authors.forename: Pekka
authors.initials: P
authors.lastname: Uimari
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Flisikowski
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.forename: Ruedi
authors.initials: R
authors.lastname: Fries
authors.forename: Marek
authors.initials: M
authors.lastname: Switonski
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000483:Alleles; D000818:Animals; D016022:Case-Control Studies; D002417:Cattle; D002465:Cell Movement / Q000235:genetics*; D002874:Chromosome Mapping / Q000662:veterinary; D056915:DNA Copy Number Variations / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005854:Germ Cells / Q000473:pathology*; D006066:Gonads / Q000473:pathology*; D008544:Melanocytes / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics